Prevention and therapy for BRCA1/2 mutation carriers and women at high risk for breast and ovarian cancer

The hereditary breast (BC) and ovarian (OC) cancer syndrome (HBOC) includes genetic alterations of various susceptibility genes such as TP53, ATM, PTE N or MSH2, MLH1, PMS1, PMS2, MSH3 and MSH6, BRCA1 and BRCA2. Germline mutat ions of the cancer-susceptibility genes BRCA1 and BRCA2 seem to be the majo r aetiology of the HBOC. Genetic counselling and identification of high-ris k families may be essential (1) to provide the best method for genetic test ing by explaining the sensitivity and specificity of the methods, (2) to of fer the opportunity to participate in specific early cancer detection progr ammes (breast (self) palpation, ultrasound, mammography and magnetic resona nce tomography for breast cancer; vaginal exploration and ultrasound for ov arian cancer), (3) to inform them about prophylactic medication (oral contr aceptive pill (OCP), chemoprevention (tamoxifen, raloxifen, aromatase inhib itors)) or surgery (bilateral prophylactic mastectomy or oophorectomy) and (4) to provide individualized psychological support. To fulfil these broad demands, an inter-disciplinary counselling approach (gynaecological oncolog y, human genetics, molecular biology, psychotherapy) in the setting of a ca ncer genetic clinic seems the most appropriate. There, participation in pre dictive genetic testing or the use of preventive or therapeutic options may be discussed extensively with the subjects. In particular, preventive opti ons are emotionally disturbing for the subjects, and in cases of previous c ancer. BC chemoprevention for high-risk women does not seem to be as effect ive as expected. However, OCP reduces the risk for OC. For prophylactic sur gery, various points have to be considered, including: (1) individual risk assessment and gain in life expectancy, (2) value of screening and early de tection methods or medical prevention, (3) disease characteristics and prog nosis, and (4) anxiety and quality of life. Decisions regarding these optio ns have to be individualized and psychological support must be offered duri ng the period of decision and follow-up. (C) 2000 Lippincott Williams & Wil kins.